IGF2R
Receptor insulinolikog faktora rasta 2 (IGF2R), znan i kao kation-neovisni receptor manoza-6-fosfata (CI-MPR) jest protein koji je kod ljudi kodiran genom IGF2R.[5][6] IGF2R je multifunkcionalni proteinski receptor koji se veže insulinski faktor rasta 2 (IGF2) na ćelijskoj površini i manoza-6-fosfat (M6P) označeni protein u trans-Golgijevoj mreži.[6]
Aminokiselinska sekvenca[uredi | uredi izvor]
Dužina polipeptidnog lanca je 2.491 aminokiselina, а molekulska težina 274.375 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MGAAAGRSPH | LGPAPARRPQ | RSLLLLQLLL | LVAAPGSTQA | QAAPFPELCS | ||||
| YTWEAVDTKN | NVLYKINICG | SVDIVQCGPS | SAVCMHDLKT | RTYHSVGDSV | ||||
| LRSATRSLLE | FNTTVSCDQQ | GTNHRVQSSI | AFLCGKTLGT | PEFVTATECV | ||||
| HYFEWRTTAA | CKKDIFKANK | EVPCYVFDEE | LRKHDLNPLI | KLSGAYLVDD | ||||
| SDPDTSLFIN | VCRDIDTLRD | PGSQLRACPP | GTAACLVRGH | QAFDVGQPRD | ||||
| GLKLVRKDRL | VLSYVREEAG | KLDFCDGHSP | AVTITFVCPS | ERREGTIPKL | ||||
| TAKSNCRYEI | EWITEYACHR | DYLESKTCSL | SGEQQDVSID | LTPLAQSGGS | ||||
| SYISDGKEYL | FYLNVCGETE | IQFCNKKQAA | VCQVKKSDTS | QVKAAGRYHN | ||||
| QTLRYSDGDL | TLIYFGGDEC | SSGFQRMSVI | NFECNKTAGN | DGKGTPVFTG | ||||
| EVDCTYFFTW | DTEYACVKEK | EDLLCGATDG | KKRYDLSALV | RHAEPEQNWE | ||||
| AVDGSQTETE | KKHFFINICH | RVLQEGKARG | CPEDAAVCAV | DKNGSKNLGK | ||||
| FISSPMKEKG | NIQLSYSDGD | DCGHGKKIKT | NITLVCKPGD | LESAPVLRTS | ||||
| GEGGCFYEFE | WHTAAACVLS | KTEGENCTVF | DSQAGFSFDL | SPLTKKNGAY | ||||
| KVETKKYDFY | INVCGPVSVS | PCQPDSGACQ | VAKSDEKTWN | LGLSNAKLSY | ||||
| YDGMIQLNYR | GGTPYNNERH | TPRATLITFL | CDRDAGVGFP | EYQEEDNSTY | ||||
| NFRWYTSYAC | PEEPLECVVT | DPSTLEQYDL | SSLAKSEGGL | GGNWYAMDNS | ||||
| GEHVTWRKYY | INVCRPLNPV | PGCNRYASAC | QMKYEKDQGS | FTEVVSISNL | ||||
| GMAKTGPVVE | DSGSLLLEYV | NGSACTTSDG | RQTTYTTRIH | LVCSRGRLNS | ||||
| HPIFSLNWEC | VVSFLWNTEA | ACPIQTTTDT | DQACSIRDPN | SGFVFNLNPL | ||||
| NSSQGYNVSG | IGKIFMFNVC | GTMPVCGTIL | GKPASGCEAE | TQTEELKNWK | ||||
| PARPVGIEKS | LQLSTEGFIT | LTYKGPLSAK | GTADAFIVRF | VCNDDVYSGP | ||||
| LKFLHQDIDS | GQGIRNTYFE | FETALACVPS | PVDCQVTDLA | GNEYDLTGLS | ||||
| TVRKPWTAVD | TSVDGRKRTF | YLSVCNPLPY | IPGCQGSAVG | SCLVSEGNSW | ||||
| NLGVVQMSPQ | AAANGSLSIM | YVNGDKCGNQ | RFSTRITFEC | AQISGSPAFQ | ||||
| LQDGCEYVFI | WRTVEACPVV | RVEGDNCEVK | DPRHGNLYDL | KPLGLNDTIV | ||||
| SAGEYTYYFR | VCGKLSSDVC | PTSDKSKVVS | SCQEKREPQG | FHKVAGLLTQ | ||||
| KLTYENGLLK | MNFTGGDTCH | KVYQRSTAIF | FYCDRGTQRP | VFLKETSDCS | ||||
| YLFEWRTQYA | CPPFDLTECS | FKDGAGNSFD | LSSLSRYSDN | WEAITGTGDP | ||||
| EHYLINVCKS | LAPQAGTEPC | PPEAAACLLG | GSKPVNLGRV | RDGPQWRDGI | ||||
| IVLKYVDGDL | CPDGIRKKST | TIRFTCSESQ | VNSRPMFISA | VEDCEYTFAW | ||||
| PTATACPMKS | NEHDDCQVTN | PSTGHLFDLS | SLSGRAGFTA | AYSEKGLVYM | ||||
| SICGENENCP | PGVGACFGQT | RISVGKANKR | LRYVDQVLQL | VYKDGSPCPS | ||||
| KSGLSYKSVI | SFVCRPEARP | TNRPMLISLD | KQTCTLFFSW | HTPLACEQAT | ||||
| ECSVRNGSSI | VDLSPLIHRT | GGYEAYDESE | DDASDTNPDF | YINICQPLNP | ||||
| MHGVPCPAGA | AVCKVPIDGP | PIDIGRVAGP | PILNPIANEI | YLNFESSTPC | ||||
| LADKHFNYTS | LIAFHCKRGV | SMGTPKLLRT | SECDFVFEWE | TPVVCPDEVR | ||||
| MDGCTLTDEQ | LLYSFNLSSL | STSTFKVTRD | SRTYSVGVCT | FAVGPEQGGC | ||||
| KDGGVCLLSG | TKGASFGRLQ | SMKLDYRHQD | EAVVLSYVNG | DRCPPETDDG | ||||
| VPCVFPFIFN | GKSYEECIIE | SRAKLWCSTT | ADYDRDHEWG | FCRHSNSYRT | ||||
| SSIIFKCDED | EDIGRPQVFS | EVRGCDVTFE | WKTKVVCPPK | KLECKFVQKH | ||||
| KTYDLRLLSS | LTGSWSLVHN | GVSYYINLCQ | KIYKGPLGCS | ERASICRRTT | ||||
| TGDVQVLGLV | HTQKLGVIGD | KVVVTYSKGY | PCGGNKTASS | VIELTCTKTV | ||||
| GRPAFKRFDI | DSCTYYFSWD | SRAACAVKPQ | EVQMVNGTIT | NPINGKSFSL | ||||
| GDIYFKLFRA | SGDMRTNGDN | YLYEIQLSSI | TSSRNPACSG | ANICQVKPND | ||||
| QHFSRKVGTS | DKTKYYLQDG | DLDVVFASSS | KCGKDKTKSV | SSTIFFHCDP | ||||
| LVEDGIPEFS | HETADCQYLF | SWYTSAVCPL | GVGFDSENPG | DDGQMHKGLS | ||||
| ERSQAVGAVL | SLLLVALTCC | LLALLLYKKE | RRETVISKLT | TCCRRSSNVS | ||||
| YKYSKVNKEE | ETDENETEWL | MEEIQLPPPR | QGKEGQENGH | ITTKSVKALS | ||||
| SLHGDDQDSE | DEVLTIPEVK | VHSGRGAGAE | SSHPVRNAQS | NALQEREDDR | ||||
| VGLVRGEKAR | KGKSSSAQQK | TVSSTKLVSF | HDDSDEDLLH | I |
Struktura[uredi | uredi izvor]
Strukturno, IGF2R je transmembranski protein tipa I (to jest, ima jedan transmembranski domen sa svojim C-terminalom na citoplazmatskoj strani lipidne membrane s velikim vanćelijskim/lumenskim domenom i relativno kratkim citoplazmatskim repom.[8] Vanćelijski domen sastoji se od male regije homologne kolagen-vezujućem domenu fibronektina i od petnaest ponavljanja sa približno 147 aminokiselinskih ostataka. Svako od ovih ponavljanja homologno je vancitoplazmatskom domenu sa 157 ostataka receptora za manozu 6-fosfat. Vezivanje za IGF2 posreduje se kroz jedno od ponavljanja, dok su dva različita ponavljanja odgovorna za vezivanje za manoza-6-fosfat. IGF2R je veličine približno 300 kDa; čini se da postoji i funkcionira kao dimer.
Funkcija[uredi | uredi izvor]
IGF2R ima funkciju uklanjanja IGF2 sa ćelijske površine radi slabljenja signalizacije i transporta lizosomnih kiselohidrolaznih prekursora iz Golgijevog aparata u lizosom. Nakon vezanja IGF2 na ćelijskoj površini, IGF2R se akumuliraju u tvoreći klatrinom obložene vezikule i internalizirane. U lumenu trans-Golgijeve mreže, IGF2R veže teret označen kao M6P.[8] IGF2R (vezani za njihov teret) prepoznaju porodicu GGA, adapterskih klatrinskih proteina i akumuliraju se u tvoreći vezikule obložene klatrinom.[9] IGF2R sa ćelijske površine i iz Golgijevog aparata šalju se u rani endosom gdje, u njegovom relativno niskom pH okruženju, IGF2R oslobađaju svoj teret. IGF2R se reciklira natrag u Golgijevom aparatu, pomoću kompleksa retromera, opet putem interakcije s GGA i vezikulama. Proteini iz terea se zatim transportuju do lizosoma, preko kasnog endosoma nezavisno od IGF2R.
Interakcije[uredi | uredi izvor]
Pokazano je da receptor faktora rasta sličan insulinu stupa u interakciju s M6PRBP1.[10][11]
Evolucija[uredi | uredi izvor]
Funkcija receptora insulinolikog faktora rasta 2 evoluirala je iz kationski neovisnog receptora manoza 6-fosfata i prvi put se vidi u Monotremata. Mjesto vezanja IGF-2 vjerovatno je stečeno slučajno, stvaranjem klastera za pojačavanje mjesta egzonske prerade u egzonu 34, što je vjerojatno bilo potrebno zbog nekoliko kilobaza insercije ponavljajućih elemenata u prethodnom intronu. Zatim je uslijedilo šestostruko sazrijevanje afiniteta tokom evolucije, podudarajući se s početkom utiskivanja i u skladu s teorijom roditeljske protivrječnosti.[12]
Također pogledajte[uredi | uredi izvor]
Reference[uredi | uredi izvor]
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- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023830 - Ensembl, maj 2017
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- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Oshima A, Nolan CM, Kyle JW, Grubb JH, Sly WS (februar 1988). "The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells". J. Biol. Chem. 263 (5): 2553–62. doi:10.1016/S0021-9258(18)69243-9. PMID 2963003.
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- ^ "UniProt, P11717" (jezik: engleski). Pristupljeno 8. 10. 2021.
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- ^ Orsel JG, Sincock PM, Krise JP, Pfeffer SR (august 2000). "Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein". Proc. Natl. Acad. Sci. U.S.A. 97 (16): 9047–51. Bibcode:2000PNAS...97.9047O. doi:10.1073/pnas.160251397. PMC 16819. PMID 10908666.
- ^ Williams C, Hoppe HJ, Rezgui D, Strickland M, Forbes BE, Grutzner F, Frago S, Ellis RZ, Wattana-Amorn P, Prince SN, Zaccheo OJ, Nolan CM, Mungall AJ, Jones EY, Crump MP, Hassan AB (novembar 2012). "Exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution". Science. 338 (6111): 1209–1213. Bibcode:2012Sci...338.1209W. doi:10.1126/science.1228633. PMC 4658703. PMID 23197533.
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Vanjski linkovi[uredi | uredi izvor]
- Insulin-Like-Growth-Factor II Receptor na US National Library of Medicine Medical Subject Headings (MeSH)